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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
52
pubmed:dateCreated
2010-12-20
pubmed:abstractText
Activation of muscarinic acetylcholine receptors (mAChRs) in the spinal cord inhibits pain transmission. At least three mAChR subtypes (M(2), M(3), and M(4)) are present in the spinal dorsal horn. However, it is not clear how each mAChR subtype contributes to the regulation of glutamatergic input to dorsal horn neurons. We recorded spontaneous excitatory postsynaptic currents (sEPSCs) from lamina II neurons in spinal cord slices from wild-type (WT) and mAChR subtype knock-out (KO) mice. The mAChR agonist oxotremorine-M increased the frequency of glutamatergic sEPSCs in 68.2% neurons from WT mice and decreased the sEPSC frequency in 21.2% neurons. Oxotremorine-M also increased the sEPSC frequency in ?50% neurons from M(3)-single KO and M(1)/M(3) double-KO mice. In addition, the M(3) antagonist J104129 did not block the stimulatory effect of oxotremorine-M in the majority of neurons from WT mice. Strikingly, in M(5)-single KO mice, oxotremorine-M increased sEPSCs in only 26.3% neurons, and J104129 abolished this effect. In M(2)/M(4) double-KO mice, but not M(2)- or M(4)-single KO mice, oxotremorine-M inhibited sEPSCs in significantly fewer neurons compared with WT mice, and blocking group II/III metabotropic glutamate receptors abolished this effect. The M(2)/M(4) antagonist himbacine either attenuated the inhibitory effect of oxotremorine-M or potentiated the stimulatory effect of oxotremorine-M in WT mice. Our study demonstrates that activation of the M(2) and M(4) receptor subtypes inhibits synaptic glutamate release to dorsal horn neurons. M(5) is the predominant receptor subtype that potentiates glutamatergic synaptic transmission in the spinal cord.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Alkaloids, http://linkedlifedata.com/resource/pubmed/chemical/Alkenes, http://linkedlifedata.com/resource/pubmed/chemical/Furans, http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid, http://linkedlifedata.com/resource/pubmed/chemical/J 104129, http://linkedlifedata.com/resource/pubmed/chemical/Muscarinic Agonists, http://linkedlifedata.com/resource/pubmed/chemical/Naphthalenes, http://linkedlifedata.com/resource/pubmed/chemical/Oxotremorine, http://linkedlifedata.com/resource/pubmed/chemical/Parasympatholytics, http://linkedlifedata.com/resource/pubmed/chemical/Piperidines, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Muscarinic, http://linkedlifedata.com/resource/pubmed/chemical/himbacine, http://linkedlifedata.com/resource/pubmed/chemical/oxotremorine M
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
24
pubmed:volume
285
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
40427-37
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Dynamic control of glutamatergic synaptic input in the spinal cord by muscarinic receptor subtypes defined using knockout mice.
pubmed:affiliation
Department of Anesthesiology and Perioperative Medicine, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural